Introduction

Background
Cavernous sinus thrombosis (CST) was initially described by Bright in 1831 as a complication of
epidural and subdural infections. CST is usually a late complication of an infection of the central
face or paranasal sinuses. Other causes include bacteremia, trauma, and infections of the ear or
maxillary teeth. CST is generally a fulminant process with high rates of morbidity and mortality.
Fortunately, the incidence of CST has been decreased greatly with the advent of effective
antimicrobial agents.

Pathophysiology
The cavernous sinuses are irregularly shaped, trabeculated cavities located at the base of the skull.
The cavernous sinuses are the most centrally located of the dural sinuses and lie on either side of the
sella turcica. These sinuses are just lateral and superior to the sphenoid sinus and are immediately
posterior to the optic chiasm (see Image 1). Each cavernous sinus is formed between layers of the
dura mater, and multiple connections exist between the 2 sinuses.
The cavernous sinuses receive venous blood from the facial veins (via the superior and inferior
ophthalmic veins) as well as the sphenoid and middle cerebral veins. They, in turn, empty into the
inferior petrosal sinuses, then into the internal jugular veins and the sigmoid sinuses via the superior
petrosal sinuses. This complex web of veins contains no valves; blood can flow in any direction
depending on the prevailing pressure gradients. Since the cavernous sinuses receive blood via this
distribution, infections of the face including the nose, tonsils, and orbits can spread easily by this
route.
The internal carotid artery with its surrounding sympathetic plexus passes through the cavernous
sinus. The third, fourth, and sixth cranial nerves are attached to the lateral wall of the sinus. The
ophthalmic and maxillary divisions of the fifth cranial nerve are embedded in the wall (see Image
1).
This intimate juxtaposition of veins, arteries, nerves, meninges, and paranasal sinuses accounts for
the characteristic etiology and presentation of CST.
Staphylococcus aureus accounts for approximately 70% of all infections. Streptococcus
pneumoniae, gram-negative bacilli, and anaerobes can also be seen. Fungi are a less common
pathogen and may include Aspergillus and Rhizopus species.

Frequency

United States
Occurrence of CST has always been low, with only a few hundred case reports in the medical
literature. The majority of these date from before the modern antibiotic era. One review of the
English-language literature found only 88 cases from 1940-1988.

Mortality/Morbidity
Prior to the advent of effective antimicrobial agents, the mortality rate from CST was effectively
100%. Typically, death is due to sepsis or central nervous system (CNS) infection. With aggressive
management, the mortality rate is now less than 30%. Morbidity, however, remains high, and
complete recovery is rare. Roughly one sixth of patients are left with some degree of visual
impairment, and one half have cranial nerve deficits.
All ages are affected, with a mean of 22 years.

Clinical

History
The early signs and symptoms of cavernous sinus thrombosis (CST) may not be specific. A patient
who presents with headache and any cranial nerve findings should be potentially evaluated for CST.
The most common signs of CST are related to the anatomical structures affected within the
cavernous sinus (see Image 1).
• Patients generally have sinusitis or a midface infection (most commonly a furuncle) for 5-10
days. In as many as 25% of cases in which a furuncle is the precipitant, it will have been
manipulated in some fashion (eg, squeezing, surgical incision).
• Headache is the most common presentation symptom and usually precedes fevers,
periorbital edema, and cranial nerve signs. The headache is usually sharp, increases
progressively, and is usually localized to the regions innervated by the ophthalmic and
maxillary branches of the fifth cranial nerve.
• In some patients, periorbital findings do not develop early on, and the clinical picture is
subtle.
• As the infection tracts posteriorly, patients complain of orbital pain and fullness
accompanied by periorbital edema and visual disturbances.
• Without effective therapy, signs appear in the contralateral eye by spreading through the
communicating veins to the contralateral cavernous sinus. Eye swelling begins as a
unilateral process and spreads to the other eye within 24-48 hours via the intercavernous
sinuses. This is pathognomonic for CST.
• The patient rapidly develops mental status changes including confusion, drowsiness, and
coma from CNS involvement and/or sepsis. Death follows shortly thereafter.

Physical
Other than the findings associated with the primary infection, the following signs are typical:
• Periorbital edema may be the earliest physical finding.
• Chemosis results from occlusion of the ophthalmic veins.
• Lateral gaze palsy (isolated cranial nerve VI) is usually seen first since CN VI lies freely
within the sinus in contrast to CN III and IV, which lie within the lateral walls of the sinus.
• Ptosis, mydriasis, and eye muscle weakness from cranial nerve III dysfunction
• Manifestations of increased retrobulbar pressure follow.
• Exophthalmos
• Ophthalmoplegia
• Signs of increased intraocular pressure (IOP) may be observed.
• Pupillary responses are sluggish.
• Decreased visual acuity is common owing to increased IOP and traction on the optic nerve
and central retinal artery.
• Hypoesthesia or hyperesthesia in dermatomes supplied by the V1 and V2 branches of the
fifth cranial nerve
• Appearance of signs and symptoms in the contralateral eye is diagnostic of CST, although
the process may remain confined to one eye.
• Meningeal signs, including nuchal rigidity and Kernig and Brudzinski signs, may be noted.
• Systemic signs indicative of sepsis are late findings. They include chills, fever, shock,
delirium, and coma.
Causes
• Most cases of septic CST are due to an acute infection in an otherwise healthy individual.
However, patients with chronic sinusitis or diabetes mellitus may be at a slightly higher risk.
• The causative agent is generally Staphylococcus aureus, although streptococci,
pneumococci, and fungi may be implicated in rare cases.
Differential Diagnoses
Cellulitis Periorbital Infections
Epidural and Subdural Sinusitis
Infections
Epidural Hematoma Subarachnoid
Hemorrhage
Glaucoma, Acute Angle- Subdural Hematoma
Closure
Orbital Infections

Other Problems to Be Considered

Carotid artery aneurysm or fistula
Exophthalmic goiter
Orbital neoplasm

Workup
Laboratory Studies
• Cavernous sinus thrombosis (CST) is a clinical diagnosis and lab studies are seldom
specific. Most patients exhibit a polymorphonuclear leukocytosis, often marked with a shift
toward immature forms. Examination of the cerebrospinal fluid is consistent with either a
parameningeal inflammation or frank meningitis. Blood culture results generally are positive
for the offending organism.

Imaging Studies
• Historically, a number of techniques have been used to image CST, including plain sinus
radiography, carotid angiography, and orbital venography. In current practice, computed
tomography (CT) scan or magnetic resonance imaging (MRI) with contrast is the modality
of choice to confirm the diagnosis of CST and to differentiate it from alternatives such as
orbital cellulitis, which may have a similar clinical presentation.
• MRI with MR venogram (MRV) is the preferred imaging choice as the MRV will show the
absence of venous flow in the affected cavernous sinus.
• On noncontrast CT, thrombosis of the cavernous sinus can be appreciated as increased
density. The introduction of intravenous contrast can reveal filling defects within the
cavernous sinus as well as thickening of the superior ophthalmic vein. Nevertheless, CT
scan findings may be subtle, and a negative CT scan cannot rule out CST reliably when the
clinical suspicion is high.
• Carotid angiography can demonstrate narrowing or obstruction of the intercavernous
segment of the carotid artery. MRI and CT scan can also show this narrowing and/or
obstruction of the carotid artery.
Procedures
• Lumbar puncture may be helpful in distinguishing CST from more localized processes (eg,
sinusitis, orbital cellulitis). Lumbar puncture reveals inflammatory cells in approximately
75% of cases.
Treatment

Emergency Department Care

• The mainstay of therapy for cavernous sinus thrombosis is early and aggressive antibiotic
administration. Although S aureus is the usual cause, broad-spectrum coverage for gram-
positive, gram-negative, and anaerobic organisms should be instituted pending the outcome
of cultures.
• Empiric antibiotic therapy should include a penicillinase-resistant penicillin plus a third- or
fourth-generation cephalosporin. If dental infection or other anaerobic infection is suspected,
an anaerobic coverage should also be added.
• IV antibiotics are recommended for a minimum of 3-4 weeks.
• Controversy exists on the use of anticoagulation for cavernous sinus thrombosis. Because of
the rarity of this syndrome, no prospective trials have been performed on the use of
anticoagulation for CST. Some retrospective studies have shown a decrease in mortality and
clot propagation by anticoagulation. Therefore, anticoagulation with heparin should be
considered since the goal is to prevent further thrombosis and to reduce the incidence of
septic emboli. Heparin is contraindicated in the presence of intracerebral hemorrhage or
other bleeding diathesis.
• Corticosteroids may help to reduce inflammation and edema and should be considered as an
adjunctive therapy. They should be instituted after antibiotic coverage. When the course of
CST leads to pituitary insufficiency, however, corticosteroids definitely are indicated to
prevent adrenal crisis. Dexamethasone or hydrocortisone should be considered.
• Surgery on the cavernous sinus is technically difficult and has never been shown to be
helpful. The primary source of infection should be drained, if feasible (eg, sphenoid
sinusitis, facial abscess). It is important to recognize the infected sphenoid sinus early and to
prevent spread of the infection to the cavernous sinus.

Consultations
If drainage is indicated, make arrangements for intensive care and request the appropriate surgical
consultation.

Medication
Antibiotic therapy ideally is started after appropriate cultures but should not be delayed if
difficulties exist in obtaining specimens. Antibiotics selected should be broad-spectrum, particularly
active against S aureus, and capable of achieving high levels in the cerebrospinal fluid. With the
recent increased prevalence of community-acquired MRSA, the emergency physician should
consider additional coverage with intravenous antibiotics, such as vancomycin, if MRSA infection
is suspected.

Antibiotic, Miscellaneous
Empiric broad-spectrum coverage for gram-positive, gram-negative, and anaerobic organisms is
necessary. Therapy must be comprehensive and should cover all likely pathogens in the context of
the clinical setting.
In cases of suspected MRSA infection, vancomycin should be added for additional coverage.
Oxacillin (Bactocill)
A bactericidal antibiotic that inhibits cell wall synthesis. Used in treatment of infections caused by
penicillinase-producing staphylococci. May be used to initiate therapy when staphylococcal
infection is suspected.
• Adult
2 g IV q4h

Pediatric
50-100 mg/kg/d PO divided q6h
150-200 mg/kg/d IV/IM divided q6h; not to exceed 12 g/d
Decreases effects of contraceptives and tetracycline; disulfiram and probenecid may increase levels;
large IV doses may increase effects of anticoagulants
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Caution in impaired renal function
Ceftriaxone (Rocephin)
Alternate antimicrobial choice. Third-generation cephalosporin that has broad gram-negative
spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant
organisms than earlier generation cephalosporins. By binding to 1 or more penicillin-binding
proteins, arrests bacterial cell wall synthesis and inhibits bacterial growth.
• Adult
2 g IV q12h

Pediatric
75 mg/kg/d IV divided bid
• Probenecid may increase levels; ethacrynic acid, furosemide, and aminoglycosides may
increase nephrotoxicity
•
Documented hypersensitivity
• Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Adjust dose in renal impairment; caution in breastfeeding women and allergy to penicillin
Metronidazole (Flagyl)
Additional anaerobic coverage. Imidazole ring-based antibiotic active against various anaerobic
bacteria and protozoa. Usually employed in combination with other antimicrobial agents (except
when used for Clostridium difficile enterocolitis, in which monotherapy appropriate).
• Adult
500 mg IV q6h
Pediatric
Not established
• increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase
toxicity; disulfiram reaction may occur with orally ingested ethanol
•
Documented hypersensitivity, first trimester of pregnancy
• Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Chloramphenicol (Chloromycetin)
Binds to 50S bacterial-ribosomal subunits and inhibits bacterial growth by inhibiting protein
synthesis. Effective against gram-negative and gram-positive bacteria.
• Adult
1.5 g IV q6h

Pediatric
50-75 mg/kg/d PO/IV divided q6h
• Barbiturates may decrease serum levels, while chloramphenicol may increase barbiturate
levels, causing toxicity; manifestations of hypoglycemia may occur with sulfonylureas;
rifampin may reduce serum levels, presumably through hepatic enzyme induction; may
increase effects of anticoagulants; may increase serum hydantoin levels, possibly resulting in
toxicity; hydantoin may increase or decrease chloramphenicol levels
• Documented hypersensitivity
• Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus

Precautions
Use only for indicated infections, or as prophylaxis for bacterial infections; serious and fatal blood
dyscrasias (eg, aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can
occur; evaluate baseline blood studies and repeat approximately every 2 d while in therapy;
discontinue upon appearance of reticulocytopenia, leukopenia, thrombocytopenia, anemia, or
findings attributable to chloramphenicol; adjust dose in liver or kidney dysfunction; caution in
pregnancy at term or during labor because of potential toxic effects on fetus (gray syndrome)
Vancomycin
Indicated for patients who cannot receive or have failed to respond to penicillins and cephalosporins
or have infections with resistant staphylococci. For abdominal penetrating injuries, it is combined
with an agent active against enteric flora and/or anaerobes.
To avoid toxicity, current recommendation is to assay vancomycin trough levels after third dose
drawn 0.5 h prior to next dosing. Use creatinine clearance to adjust dose in patients diagnosed with
renal impairment.
Used in conjunction with gentamicin for prophylaxis in penicillin allergic patients undergoing
gastrointestinal or genitourinary procedures.
• 1 g or 15 mg/kg IV q12h
Pediatri
30-40 mg/kg/d IV in 2 doses
Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with
anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase
above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced
when coadministered with nondepolarizing muscle relaxants
• documented hypersensitivity
• Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus
Precautions
Caution in renal failure, neutropenia; red man syndrome is caused by too rapid IV infusion (dose
given over a few min) but rarely happens when dose given IV over 2 h administration or as PO or
IP administration; red man syndrome is not an allergic reaction

Anticoagulants
Unfractionated IV heparin and fractionated low-molecular-weight SC heparins are the 2 options in
anticoagulation therapy.
Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not
actively lyse thrombus but able to inhibit further thrombogenesis. Prevents reaccumulation of clot
after spontaneous fibrinolysis. Various dosing nomograms available.
Adult
80 U/kg IV bolus; then 18 U/kg/h IV infusion; titrate to desired aPTT
Pediatric
Administer as in adults
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran,
dipyridamole, and hydroxychloroquine may increase toxicity
Documented hypersensitivity; subacute bacterial endocarditis; intracerebral hemorrhage, bleeding
diathesis, or other active bleeding; history of heparin-induced thrombocytopenia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if
benefits outweigh risk to fetus
Precautions
In neonates, preservative-Free heparin is recommended to avoid possible toxicity (gasping
syndrome) by benzyl alcohol, which is used as preservative; caution in severe hypotension and
shock; monitor for bleeding in peptic ulcer disease, menstruation, increased capillary permeability,
and when giving IM injections
Corticosteroids
These agents have anti-inflammatory properties and cause profound and varied metabolic effects.
They modify the body's immune response to diverse stimuli. When the course of CST leads to
pituitary insufficiency, corticosteroids definitely are indicated to prevent adrenal crisis.
Hydrocortisone (Solu-Cortef, Westcort)
DOC due to its mineralocorticoid activity and glucocorticoid effects. Decreases inflammation by
suppressing migration of polymorphonuclear leukocytes and reversing increased capillary
permeability. Useful in management of inflammation caused by an immune response.
Adult
100 mg IV q6h
Pediatric
Infants and young children: 1-2 mg/kg IV as bolus followed by 25-150 mg/d divided q6-8h
• Clearance may decrease with estrogens; may increase digitalis toxicity secondary to
hypokalemia
• Documented hypersensitivity; viral, fungal, or tubercular skin infections
• Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Abrupt discontinuation of glucocorticoids may cause adrenal crisis; caution in hyperthyroidism,
osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis
Follow-up

Further Inpatient Care

• Admission to intensive care unit is indicated.
• Deterrence/Prevention
• Patients should be educated that furuncles or abscesses (pimples) in the central portion of
the face should not be manipulated without prior antibiotic coverage.

Complications
• Meningitis
• Septic emboli
• Blindness
• Cranial nerve palsies
• Sepsis and shock

Prognosis
• Mortality rate is as high as 30%; the majority of survivors suffer permanent sequelae.
• Medicolegal Pitfalls
• Failure to consider CST in the differential diagnosis of sinusitis, facial, or periorbital
cellulitis